Zoltan Szekanecz

Publications of Zoltan Szekanecz

• Peripheral Blood Gene Expression and IgG Glycosylation Profiles as Markers of Tocilizumab Treatment in Rheumatoid Arthritis.

  Authors: Bertalan Mesko, Szilard Poliska, Szilvia Szamosi, Zoltan Szekanecz, Janos Podani, Csaba Varadi, Andras Guttman, Laszlo Nagy

  The Journal of rheumatology. 04/2012;

  OBJECTIVE: Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is notOBJECTIVE: Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment. METHODS: Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG Nglycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders. RESULTS: Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline. CONCLUSION: As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.

• Immune-regulatory mechanisms in systemic autoimmune and rheumatic diseases.

  Authors: Britt Nakken, Philip Alex, Ludvig Munthe, Zoltan Szekanecz, Peter Szodoray

  Clinical & developmental immunology. 01/2012; 2012:957151.

• B-cells and their targeting in rheumatoid arthritis--current concepts and future perspectives.

  Authors: Britt Nakken, Ludvig A Munthe, Yrjö T Konttinen, Anna Klokk Sandberg, Zoltan Szekanecz, Philip Alex, Peter Szodoray

  Autoimmunity reviews. 07/2011; 11(1):28-34.

  Rheumatoid arthritis (RA) is a chronic, autoimmune disease that affects primarily the joints and without proper treatment results in their progressive destruction. In addition to T-cells, B-cellsRheumatoid arthritis (RA) is a chronic, autoimmune disease that affects primarily the joints and without proper treatment results in their progressive destruction. In addition to T-cells, B-cells play a central role in the pathogenesis of this disease. The synovial tissue is an active site of B-cell accumulation, plasma cell differentiation and in situ antibody-production in RA. As part of the complex role of B-cells in the joints and synovial membrane of RA patients, B cells secrete chemokines and cytokines and may function as antigen presenting cells. The multifaceted pathogenic function of B-cells identifies them as excellent targets for immunosuppressive therapy. B-cell targeting involves a wide spectrum of molecules, for example the B-cell antigen CD20 that allows specific and effective B-cell depletion. Another target, CD79, expressed by B-cell and plasma cell precursors is an obvious candidate that induces apoptosis as well as inhibition of B-cell receptor (BCR) activation and possibly depletion of ectopic germinal centers (GC). Inhibition of B-cell co-stimulatory molecules such as CD40, CD80/86 and ICOS, can lead to diminished B-cell activation. Moreover, anti-chemokine and anti-cytokine therapies can be efficacious in RA by the disruption of B-cell activation and autoantibody production, B-cell synovial migration and ectopic GC formation. Finally, targeting the signal transduction pathways required for proximal BCR signaling has also been found efficacious in early clinical trials in RA. Even so, some B cells inhibit immune responses, these regulatory B cells may play a part in immune regulation in patients and it is unclear what effects B cell depletion strategies have in terms of such B cell subsets. This review discusses current strategies of targeting B-cells as therapeutic candidates in the management of RA. Better insights into the pathogenic role of B-cells provide efficacious opportunities to improve both therapy and prognosis of patients with RA.

• Hyperferritinemia is Associated with Serologic Antiphospholipid Syndrome in SLE Patients.

  Authors: Gisele Zandman-Goddard, Hedi Orbach, Nancy Agmon-Levin, Mona Boaz, Howard Amital, Zoltan Szekanecz, Gabriella Szucs, Josef Rovensky, Emese Kiss, Nadia Corocher, Andrea Doria, Ljudmila Stojanovich, Francesca Ingegnoli, Pier Luigi Meroni, Blaz Rozman, Jesus Gomez-Arbesu, Miri Blank, Yehuda Shoenfeld

  Clinical reviews in allergy & immunology. 03/2011;

  Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort.Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM) > 2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6 ± 7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p = 0.003) and lupus anticoagulant (11.3% vs. 29.0%, p = 0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7 ± 369 vs. 30.9 ± 17.3 GPI, p = 0.02) and aCL IgM antibody levels (75.3 ± 357.4 vs. 9.3 ± 10.3 GPI, p = 0.02), and marginally lower aCL IgG antibody levels (9.2 ± 4.9 vs. 9.7 ± 3.9 GPI, p = 0.096). While the ECLAM score significantly correlated with hyperferritinemia (p = 0.04), the SLEDAI score was marginally associated with hyperferritinemia (p = 0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients.

• Prolactin and Autoimmunity : Hyperprolactinemia Correlates with Serositis and Anemia in SLE Patients.

  Authors: Hedi Orbach, Gisele Zandman-Goddard, Mona Boaz, Nancy Agmon-Levin, Howard Amital, Zoltan Szekanecz, Gabriella Szucs, Josef Rovensky, Emese Kiss, Andrea Doria, Anna Ghirardello, Jesus Gomez-Arbesu, Ljudmila Stojanovich, Francesca Ingegnoli, Pier Luigi Meroni, Blaz' Rozman, Miri Blank, Yehuda Shoenfeld

  Clinical reviews in allergy & immunology. 02/2011;

  Evidence points to an association of prolactin to autoimmune diseases. We examined the correlation between hyperprolactinemia and disease manifestations and activity in a large patient cohort. Age-Evidence points to an association of prolactin to autoimmune diseases. We examined the correlation between hyperprolactinemia and disease manifestations and activity in a large patient cohort. Age- and sex-adjusted prolactin concentration was assessed in 256 serum samples from lupus patients utilizing the LIASON prolactin automated immunoassay method (DiaSorin S.p.A, Saluggia, Italy). Disease activity was defined as present if European Consensus Lupus Activity Measurement (ECLAM) > 2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 4. Lupus manifestations were grouped by organ involvement, laboratory data, and prescribed medications. Hyperprolactinemia was presented in 46/256 (18%) of the cohort. Hyperprolactinemic patients had significantly more serositis (40% vs. 32.4%, p = 0.03) specifically, pleuritis (33% vs. 17%, p = 0.02), pericarditis (30% vs. 12%, p = 0.002), and peritonitis (15% vs. 0.8%, p = 0.003). Hyperprolactinemic subjects exhibited significantly more anemia (42% vs. 26%, p = 0.02) and marginally more proteinuria (65.5% vs. 46%, p = 0.06). Elevated levels of prolactin were not significantly associated with other clinical manifestations, serology, or therapy. Disease activity scores were not associated with hyperprolactinemia. Hyperprolactinemia in lupus patients is associated with all types of serositis and anemia but not with other clinical, serological therapeutic measures or with disease activity. These results suggest that dopamine agonists may be an optional therapy for lupus patients with hyperprolactinemia.

• Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature.

  Authors: Yoav Arnson, Howard Amital, Nancy Agmon-Levin, Danny Alon, María Sánchez-Castañón, Marcos López-Hoyos, Marco Matucci-Cerinic, Gabriella Szücs, Yinon Shapira, Zoltan Szekanecz, Yehuda Shoenfeld

  Autoimmunity reviews. 02/2011; 10(8):490-4.

  Low vitamin D serum concentrations have been reported in several autoimmune conditions. The study's aim was to explore such a relationship in a large multinational population of patients withLow vitamin D serum concentrations have been reported in several autoimmune conditions. The study's aim was to explore such a relationship in a large multinational population of patients with systemic sclerosis (SSc) and to pursue possible clinical and laboratory correlates with vitamin D concentrations. 327 sera samples of European patients with SSc and 141 samples of compatible healthy controls were studied for vitamin D concentrations using the commercial kit LIAISON 25-OH vitamin D assay (Diasorin). Additionally, clinical parameters including the Rodnan skin score, diffusing lung capacity for carbon monoxide (DLCO), systolic pulmonary artery pressure (sPAP), forced vital capacity (FVC), and nailfold video capillaroscopic, erythrocyte sedimentation rate (ESR), anti-nuclear antibodies (ANA and scl70), rheumatoid factor (RF) were investigated. Vitamin D serum concentration was 13.5 ± 9.0 ng/ml (mean ± standard deviation) in patients with SSc compared to 21.6 ± 9.7 ng/ml in a control group (p<0.001). A negative correlation between patients' age and vitamin D concentration (r = -0.2, p<0.05, n = 96) was observed. An inverse relationship was found between skin involvement and vitamin D serum concentrations; Patients with a Rodnan skin score of 10 or lower (n = 11) had a mean vitamin D concentration of 17.7 ± 10.4 ng/ml compared to patients with a score above 10 (n = 28) 8 ± 10.1 ng/ml (p=0.02, by the Mann-Whitney test). In conclusion, Patients with SSc have significantly lower serum vitamin D concentrations compared to healthy controls; moreover fibrosis of the cutaneous tissue is inversely related to the vitamin D concentration.

• Ferritin and prolactin levels in multiple sclerosis.

  Authors: Rafael Da Costa, Martine Szyper-Kravitz, Zoltan Szekanecz, Tünde Csépány, Katalin Dankó, Yinon Shapira, Gisele Zandman-Goddard, Hedi Orbach, Nancy Agmon-Levin, Yehuda Shoenfeld

  The Israel Medical Association journal : IMAJ. 02/2011; 13(2):91-5.

  Multiple sclerosis (MS) is a common demyelnating disorder of the central nervous system (CNS) and ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical formsMultiple sclerosis (MS) is a common demyelnating disorder of the central nervous system (CNS) and ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity. To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease. Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls. Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P < 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary-progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing-progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05) Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.

• Vitamin D and autoimmune thyroid diseases.

  Authors: Shaye Kivity, Nancy Agmon-Levin, Michael Zisappl, Yinon Shapira, Endre V Nagy, Katalin Dankó, Zoltan Szekanecz, Pnina Langevitz, Yehuda Shoenfeld

  Cellular & molecular immunology. 01/2011; 8(3):243-7.

  The role of vitamin D as an immune modulator has been emphasized in recent years, and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemicThe role of vitamin D as an immune modulator has been emphasized in recent years, and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus erythematosus. Vitamin D mediates its effect though binding to vitamin D receptor (VDR), and activation of VDR-responsive genes. While VDR gene polymorphism was found to associate with autoimmune thyroid diseases (AITDs), few studies examined levels of vitamin D in these patients and those that did yielded conflicting results. We therefore undertook to evaluate the levels of vitamin D in patients with AITDs compared to patients with non-AITDs and healthy controls. Serum vitamin D (25-OH) levels were measured in 50 patients with AITDs, 42 patients with non-AITDs and 98 healthy subjects, utilizing the LIAISON chemiluminescence immunoassay (DiaSorin, Saluggia, Italy). Vitamin D deficiency was designated at levels lower than 10 ng/ml. Antithyroid antibodies, thyroid functions and demographic parameters were evaluated in all patients. The prevalence of vitamin D deficiency was significantly higher in patients with AITDs compared with healthy individuals (72% versus 30.6%; P<0.001), as well as in patients with Hashimoto's thyroiditis compared to patients with non-AITDs (79% versus 52%; P<0.05). Vitamin D deficiency also correlated to the presence of antithyroid antibodies (P=0.01) and abnormal thyroid function tests (P=0.059). Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests, suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.

• Relationship between rheumatoid factor isotypes and IgG anti-cyclic citrullinated peptide antibodies.

  Authors: Troy D Jaskowski, Harry R Hill, Katherine L Russo, Gabriella Lakos, Zoltan Szekanecz, Marius Teodorescu

  The Journal of rheumatology. 08/2010; 37(8):1582-8.

  To validate in a general patient population (GPP) the clinical value of measuring rheumatoid factor (RF) isotypes in relationship to IgG anti-cyclic citrullinated peptide (CCP) antibodies (CCP2 andTo validate in a general patient population (GPP) the clinical value of measuring rheumatoid factor (RF) isotypes in relationship to IgG anti-cyclic citrullinated peptide (CCP) antibodies (CCP2 and CCP3). Serum samples were obtained as follows: 1021 GPP, for whom RF was ordered for diagnosis, 137 with rheumatoid arthritis (RA), 100 healthy blood donors (HBD), and 50 with systemic lupus erythematosus. Turbidimetry and ELISA were utilized for RF screening, and individual RF isotypes and IgG anti-CCP antibodies were measured by ELISA; RF IgG was measured after pepsin digestion. We validated the generally accepted 90%-98% positive predictive value (PPV) and about 68% sensitivity of the anti-CCP2 test on our diagnosed cohorts as 96% (95% CI 89-99) and 65% (95% CI 56-73), respectively. The 282 RF IgM+ specimens identified in the GPP were subdivided into 3 subsets: (1) 83 as RF IgM+ IgG+ IgA+ with 63% (95% CI 51-73) anti-CCP2+ (i.e., sensitivity similar to the RA cohort); (2) 50 as RF IgM+ IgG- IgA+ with significantly fewer anti-CCP2+ (22%; 95% CI 12-36); and (3) about half as IgM+ IgG- IgA- with just 3% (95% CI 1-8) anti-CCP2+, i.e., not significantly different from the 1% (95% CI 0-5) in HBD. Thus, the chance for a specimen in the GPP to be anti-CCP2+ (i.e., to come from an RA patient) was increased by 7- and 21-fold, respectively, by identifying RF IgA and IgG in addition to IgM. About one-third of anti-CCP- RA patients in our cohort were RF IgM+ IgG+ IgA+, reflected as 3.4% in the anti-CCP2- GPP. The agreement between anti-CCP2 and anti-CCP3 was significantly higher for RF+ RA and GPP patients, 86% (95% CI 78-93) and 83% (95% CI 73-91), respectively, than for the RF- RA (27%; 95% CI 6-61), RF- GPP (4%; 95% CI 0-19), and non-RA controls. Anti-CCP2 but not anti-CCP3 significantly distinguished the HBD from the GPP (95% CI). Measurement of the 3 isotypes of RF may increase by 7- to 21-fold the chance of making the serologic diagnosis of RA; a testing algorithm is proposed. The anti-CCP antibody response appears significantly less peptide-specific in the presence of IgM RF than in its absence.

• Chemokines and chemokine receptors in arthritis.

  Authors: Zoltan Szekanecz, Aniko Vegvari, Zoltan Szabo, Alisa E Koch

  Frontiers in bioscience (Scholar edition). 01/2010; 2:153-67.

  Chemokines are involved in leukocyte recruitment to inflammatory sites, such as the synovial tissue in rheumatoid arthritis (RA). There is a structural and a functional classification of chemokines.Chemokines are involved in leukocyte recruitment to inflammatory sites, such as the synovial tissue in rheumatoid arthritis (RA). There is a structural and a functional classification of chemokines. The former includes four groups: CXC, CC, C and CX3C chemokines. Chemokines may also be either inflammatory or homeostatic, however, these functions often overlap. Anti-chemokine and anti-chemokine receptor targeting may be therapeutically used in the future biological therapy of arthritis. Most data in this field have been obtained from animal models of arthritis as only very few human RA trials have been completed. However, it is very likely that various specific chemokine and chemokine receptor antagonists will be developed and administered to RA patients.

• Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets.

  Authors: Bertalan Mesko, Szilard Poliska, Andrea Szegedi, Zoltan Szekanecz, Karoly Palatka, Maria Papp, Laszlo Nagy

  BMC medical genomics. 01/2010; 3:15.

  Chronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, butChronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, but their pathogenesis is still not well understood. It is also not well known if distinct changes in gene expression characterize these diseases and if these patterns can discriminate between diseased and control patients and/or stratify the disease. The main focus of our work was the identification of novel markers that overlap among the 3 diseases or discriminate them from each other. Diseased (n = 13, n = 15 and n = 12 in IBD, psoriasis and RA respectively) and healthy patients (n = 18) were recruited based on strict inclusion and exclusion criteria; peripheral blood samples were collected by clinicians (30 ml) in Venous Blood Vacuum Collection Tubes containing EDTA and peripheral blood mononuclear cells were separated by Ficoll gradient centrifugation. RNA was extracted using Trizol reagent. Gene expression data was obtained using TaqMan Low Density Array (TLDA) containing 96 genes that were selected by an algorithm and the statistical analyses were performed in Prism by using non-parametric Mann-Whitney U test (P-values < 0.05). Here we show that using a panel of 96 disease associated genes and measuring mRNA expression levels in peripheral blood derived mononuclear cells; we could identify disease-specific gene panels that separate each disease from healthy controls. In addition, a panel of five genes such as ADM, AQP9, CXCL2, IL10 and NAMPT discriminates between all samples from patients with chronic inflammation and healthy controls. We also found genes that stratify the diseases and separate different subtypes or different states of prognosis in each condition. These findings and the identification of five universal markers of chronic inflammation suggest that these diseases have a common background in pathomechanism, but still can be separated by peripheral blood gene expression. Importantly, the identified genes can be associated with overlapping biological processes including changed inflammatory response. Gene panels based on such markers can play a major role in the development of personalized medicine, in monitoring disease progression and can lead to the identification of new potential drug targets in chronic inflammation.

• Chemokines and angiogenesis in rheumatoid arthritis.

  Authors: Zoltan Szekanecz, Angela Pakozdi, Agnes Szentpetery, Timea Besenyei, Alisa E Koch

  Frontiers in bioscience (elite edition). 02/2009; 1:44-51.

  In rheumatoid arthritis, chemokines mediate the migration of inflammatory leukocytes into the synovium. Among the four known chemokine families, CXC, CC chemokines and fractalkine seem to be ofIn rheumatoid arthritis, chemokines mediate the migration of inflammatory leukocytes into the synovium. Among the four known chemokine families, CXC, CC chemokines and fractalkine seem to be of outstanding importance in this process. Angiogenesis, the formation of new vessels, is also important during the perpetuation of inflammation underlying rheumatoid arthritis. In this review, authors discuss the role of the most important chemokines and chemokine repetors in arthritis-associated neovascularization. The process and regulation of angiogenesis are described in this context as well. Apart from discussing the pathogenic role of chemokines and chemokine receptors in arthritic vessel formation, authors also review the important relevance of chemokines and angiogenesis for therapeutic intervention.

• Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases.

  Authors: Hedi Orbach, Gisele Zandman-Goddard, Howard Amital, Vivian Barak, Zoltan Szekanecz, Gabriella Szucs, Katalin Danko, Endre Nagy, Tunde Csepany, Jozelio F Carvalho, Andrea Doria, Yehuda Shoenfeld

  Annals of the New York Academy of Sciences. 09/2007; 1109:385-400.

  The development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigenThe development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen (TPA) were measured in autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis (PM), dermatomyositis (DM), multiple sclerosis (MS), autoimmune thyroid diseases, and antiphospholipid syndrome. Hyperprolactinemia (HPRL) was detected in 24% of PM patients, in 21% of SLE patients, in 6.7% of MS patients, 6% of RA patients, and in 3% of SSc patients. Hyperferritinemia was detected in 23% of SLE patients, 15% of DM patients, 8% of MS patients, and 4% of RA patients. The patients had relatively low levels of 25 OH Vitamin D: the average results (mean +/- SD) were between 9.3 +/- 4.4 to 13.7 +/- 7.1 ng/mL in the different diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL are regarded as deficient. TPA levels were in the same range of the controls, elevated only in SLE. HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels did not correlate with SLE activity elevated levels of rheumatoid factor or anti-CCP antibodies in RA. HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications in the pathogenesis of the autoimmune diseases. Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be considered in certain cases. Hyperferritinemia may be used as an acute-phase reactant marker in autoimmune diseases mainly SLE. TPA may be used to indicate the tendency for malignancies.

• Gene expression profiles of systemic lupus erythematosus and rheumatoid arthritis.

  Authors: Michael Centola, Zoltan Szekanecz, Emese Kiss, Margit Zeher, Gyula Szegedi, Britt Nakken, Peter Szodoray

  Expert review of clinical immunology. 09/2007; 3(5):797-806.

  Gene expression profiling using microarray technology is being employed to define specific molecular mediators and pathways involved in immunobiology, to understand the intricate interplay of genesGene expression profiling using microarray technology is being employed to define specific molecular mediators and pathways involved in immunobiology, to understand the intricate interplay of genes participating in the pathogenesis, and to develop biomarkers of disease activity in both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This review summarizes the latest information on the pathogenesis of SLE and RA and describes the utilization of microarray technology in these systemic autoimmune diseases.

• Immunoperoxidase histochemistry for the detection of cellular adhesion molecule, cytokine, and chemokine expression in the arthritic synovium.

  Authors: Zoltan Szekanecz, Alisa E Koch

  Methods in molecular biology (Clifton, N.J.). 02/2003; 225:283-90.

• Disturbances in B- and T-cell homeostasis in rheumatoid arthritis: Suggested relationships with antigen-driven immune responses

  Authors: Andrea Fekete, Lilla Soos, Zoltan Szekanecz, Zoltan Szabo, Peter Szodoray, Sandor Barath, Gabriella Lakos

  Journal of Autoimmunity.

  Naïve and memory B- and T-cell subsets were examined with three-color flow cytometry in the peripheral blood of patients with rheumatoid arthritis (RA) in comparison with healthy controls, and theirNaïve and memory B- and T-cell subsets were examined with three-color flow cytometry in the peripheral blood of patients with rheumatoid arthritis (RA) in comparison with healthy controls, and their association with disease duration, activity and autoantibodies was investigated in order to reveal potential imprints of antigen-specific immune response in RA. The B-cell population consisted of significantly less naïve (58.1 ± 3.9% versus 68.7 ± 3.7%; p = 0.04), and more IgD−/CD27+ memory B cells (19.6 ± 2.1% versus 13.7 ± 2.1%; p = 0.04) compared to healthy subjects. In addition, strong correlation was demonstrated between disease duration and the percentage of memory B cells (p < 0.0001). Increased CD8+ terminally differentiated effector memory/central memory T-cell ratio (1.35 ± 0.35 versus 0.84 ± 0.24) was also detected in RA patients compared with controls, which also correlated with the duration of RA (p = 0.005). The frequency of memory B cells and CD8+ effector memory T cells correlated with the proportion of CD4+ effector memory lymphocytes, suggesting cooperation between immune cells. Our results reflect disturbances in B- and T-cell homeostasis characterized by the accumulation of memory B cells and a shift towards CD8+ terminally differentiated effector memory T cells in RA, suggesting ongoing, antigen-driven immune response and accelerated differentiation of B and T lymphocytes into effector cells.

• Disturbances in B- and T-cell homeostasis in rheumatoid arthritis: suggested relationships with antigen-driven immune responses.

  Authors: Andrea Fekete, Lilla Soos, Zoltan Szekanecz, Zoltan Szabo, Peter Szodoray, Sandor Barath, Gabriella Lakos

  Journal of autoimmunity. 29(2-3):154-63.

  Naïve and memory B- and T-cell subsets were examined with three-color flow cytometry in the peripheral blood of patients with rheumatoid arthritis (RA) in comparison with healthy controls, and theirNaïve and memory B- and T-cell subsets were examined with three-color flow cytometry in the peripheral blood of patients with rheumatoid arthritis (RA) in comparison with healthy controls, and their association with disease duration, activity and autoantibodies was investigated in order to reveal potential imprints of antigen-specific immune response in RA. The B-cell population consisted of significantly less naïve (58.1+/-3.9% versus 68.7+/-3.7%; p=0.04), and more IgD-/CD27+ memory B cells (19.6+/-2.1% versus 13.7+/-2.1%; p=0.04) compared to healthy subjects. In addition, strong correlation was demonstrated between disease duration and the percentage of memory B cells (p<0.0001). Increased CD8+ terminally differentiated effector memory/central memory T-cell ratio (1.35+/-0.35 versus 0.84+/-0.24) was also detected in RA patients compared with controls, which also correlated with the duration of RA (p=0.005). The frequency of memory B cells and CD8+ effector memory T cells correlated with the proportion of CD4+ effector memory lymphocytes, suggesting cooperation between immune cells. Our results reflect disturbances in B- and T-cell homeostasis characterized by the accumulation of memory B cells and a shift towards CD8+ terminally differentiated effector memory T cells in RA, suggesting ongoing, antigen-driven immune response and accelerated differentiation of B and T lymphocytes into effector cells.

• Angiogenesis and chemokines in rheumatoid arthritis and other systemic inflammatory rheumatic diseases.

  Authors: Edit Bodolay, Alisa E Koch, Joon Kim, Gyula Szegedi, Zoltan Szekanecz

  Journal of cellular and molecular medicine. 6(3):357-76.

  Angiogenesis, the formation of new vessels, is important in the pathogenesis of rheumatoid arthritis (RA) and other inflammatory diseases. Chemotactic cytokines termed chemokines mediate the ingressAngiogenesis, the formation of new vessels, is important in the pathogenesis of rheumatoid arthritis (RA) and other inflammatory diseases. Chemotactic cytokines termed chemokines mediate the ingress of leukocytes, including neutrophils and monocytes into the inflamed synovium. In this review, authors discuss the role of the most important angiogenic factors and angiogenesis inhibitors, as well as relevant chemokines and chemokine receptors involved in chronic inflammatory rheumatic diseases. RA was chosen as a prototype to discuss these issues, as the majority of studies on the role of angiogenesis and chemokines in inflammatory diseases were carried out in arthritis. However, other systemic inflammatory (autoimmune) diseases including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), polymyositis/dermatomyositis (PM/DM) and systemic vasculites are also discussed in this context. As a number of chemokines may also play a role in neovascularization, this issue is also described here. Apart from discussing the pathogenic role of angiogenesis and chemokines, authors also review the regulation of angiogenesis and chemokine production by other inflammatory mediators, as well as the important relevance of neovascularization and chemokines for antirheumatic intervention.

• Cell-cell interactions in synovitis: Endothelial cells and immune cell migration

  Authors: Zoltan Szekanecz, Alisa E Koch

  Leukocyte ingress into the synovium is a key process in the pathogenesis of rheumatoid arthritis and other inflammatory conditions. In this review, the role of endothelial cells in leukocyteLeukocyte ingress into the synovium is a key process in the pathogenesis of rheumatoid arthritis and other inflammatory conditions. In this review, the role of endothelial cells in leukocyte extravasation will be discussed, including the role of the most relevant cellular adhesion molecules. These molecules play an important role in mediating leukocyte-endothelial interactions. It is likely that different adhesive pathways are involved in different steps of leukocyte adhesion to and migration through endothelia. Targeting of pathological endothelial function, including leukocyte-endothelial adhesion, may be useful for the future management of inflammatory arthritis.

• Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: A retrospective cohort study and review of the literature

  Authors: Yoav Arnson, Howard Amital, Nancy Agmon-Levin, Danny Alon, María Sánchez-Castañón, Marcos López-Hoyos, Marco Matucci-Cerinic, Gabriella Szücs, Yinon Shapira, Zoltan Szekanecz, Yehuda Shoenfeld

  Autoimmunity Reviews.

  Low vitamin D serum concentrations have been reported in several autoimmune conditions. The study's aim was to explore such a relationship in a large multinational population of patients withLow vitamin D serum concentrations have been reported in several autoimmune conditions. The study's aim was to explore such a relationship in a large multinational population of patients with systemic sclerosis (SSc) and to pursue possible clinical and laboratory correlates with vitamin D concentrations.327 sera samples of European patients with SSc and 141 samples of compatible healthy controls were studied for vitamin D concentrations using the commercial kit LIAISON 25-OH vitamin D assay (Diasorin). Additionally, clinical parameters including the Rodnan skin score, diffusing lung capacity for carbon monoxide (DLCO), systolic pulmonary artery pressure (sPAP), forced vital capacity (FVC), and nailfold video capillaroscopic, erythrocyte sedimentation rate (ESR), anti-nuclear antibodies (ANA and scl70), rheumatoid factor (RF) were investigated.Vitamin D serum concentration was 13.5 ± 9.0 ng/ml (mean ± standard deviation) in patients with SSc compared to 21.6 ± 9.7 ng/ml in a control group (p < 0.001). A negative correlation between patients' age and vitamin D concentration (r = − 0.2, p < 0.05, n = 96) was observed. An inverse relationship was found between skin involvement and vitamin D serum concentrations; Patients with a Rodnan skin score of 10 or lower (n = 11) had a mean vitamin D concentration of 17.7 ± 10.4 ng/ml compared to patients with a score above 10 (n = 28) 8 ± 10.1 ng/ml (p = 0.02, by the Mann–Whitney test).In conclusion, Patients with SSc have significantly lower serum vitamin D concentrations compared to healthy controls; moreover fibrosis of the cutaneous tissue is inversely related to the vitamin D concentration.